The lantibiotic nisin is a 34-residue bacteriocin produced by the Gram-positive bacteria Lactococcus lactis spp. It is first ribosomally synthesized as an inactive precursor which is then post-translationally modified into its mature biologically active form. Described herein is a two-part study investigating (1) the structural basis of how the characteristic nisin lanthionine rings are installed by the enzyme NisC and (2) how Lactococcus lactis spp., despite producing an effective bacteriocin like nisin, is resistant to the toxic effects of nisin. The results described here together provide the first structural insights into the biosynthesis of nisin as well as insights into how L. lactis demonstrates autoimmunity to the lantibiotic nisin.